As the dosage form of vaccine preparations, most of the commercial products that are currently available are injections. An injectable vaccine induces the blood (systemic) immune response (production of an IgG antibody), but does not induce the immune response (production of an IgA antibody) in mucous membranes, and hence has a problem of difficulty in preventing the infection itself with a pathogen via the mucosal pathway although proliferation of the pathogen after infection can be prevented.
In light of this, recently, vaccination from mucous membranes attracts attention, and among others, development of a mucosal administration (transnasal administration) type vaccine using an influenza virus as an antigen is in the limelight.
A mucosal administration type vaccine is capable of inducing not only the systemic immunity (production of an IgG antibody) but also the mucosal immunity (production of an IgA antibody). The IgA antibody is featured by not distinguishing the type of the pathogen of the objective disease so strictly, and being capable of responding to change in the prevailing type of the pathogen that changes every year, and hence it is considered as being effective for preventing a pandemic.
The transnasal administration type vaccine is in the limelight partly because administration of an antigen to a nasal mucous membrane is not affected by gastric acid and protease, while administration of an antigen to a mucous membrane of a digestive tract is likely to be affected by these, and the affection is difficult to be avoided. Further, on a nasal mucous membrane, there is an antigen recognizing tissue called NALT, and this is also a reason why the transnasal administration type vaccine is effective on the immune response.
However, administration of an antigen to the nasal mucous membrane has a high possibility of a severe side effect such as acute encephalopathy although it is highly effective. Also it has the problems that transnasal administration itself is cumbersome and difficult for the aged, infants and so on, and stable effects cannot be obtained due to physical factors such as a running nose.
On the other hand, the attempt to orally administer an antigen, and following swallowing, to induce the systemic immunity and the mucosal immunity in the mucous membrane of the digestive tract (small intestine) or the like has often been made. The problem in such an attempt lies in how digestion of the antigen by gastric acid and digestion of the antigen by protease are prevented. For solving such a problem, a technique of incorporating a large quantity of an antacid for neutralizing the gastric acid, or a technique for protecting an antigen by a coating technique such as a microsphere have been developed.
However, a technique that has been actually successful is based on live attenuated poliovirus vaccines or live attenuated rotavirus vaccines that are originally highly stable in the gastric acid.
As an example of inducing the mucosal immunity and the systemic immunity in the intraoral mucosal route, the following reports have been made.
Patent Literature 1 proposes an immunogenic composition containing one or more antigens and a Toll-like receptor (TLR) agonist in an oral (for example, sublingual administration) composition, and discloses an influenza antigen as an antigen, and a TLR4 agonist as an adjuvant.
However, the TLR4 agonist in the immunogenic composition proposed in Patent Literature 1 has weak effect in terms of the immune induction, and hence, an adjuvant that is capable of inducing stronger immunity and is safe has been demanded.
Also, Patent Literature 2 proposes a lipopolysaccharide (LPS) derived from Pantoea bacteria, and describes that the LPS is safer than conventional LPSs, and the immune reaction is enhanced when it is administered together with an antigen.
Patent Literature 2, however, lacks distinct reference and illustration regarding the use for acquired immunity, and also lacks reference to the optimum ratio of adjuvant/antigen. Further, Patent Literature 2 lacks distinct reference regarding use of an LPS derived from Pantoea bacteria as a mucosal vaccine.
Also, Patent Literature 3 proposes a vaccine containing a combination of Poly(I:C) and zymosan as an inactivated antigen of a pathogen, and an immunostimulant (adjuvant), and describes an example of using a lipopolysaccharide (LPS) derived from Pantoea agglomerans as an adjuvant, and an influenza virus as a pathogen.
In the example of the vaccine containing a lipopolysaccharide (LPS) derived from Pantoea agglomerans described in Patent Literature 3, the vaccine is administered to a nasal mucous membrane, and there is no teaching about administration to a specific mucous membrane such as an intraoral mucous membrane. Generally, it is the common knowledge in the art that the effective adjuvant differs depending on the administration site. Therefore, it is unclear whether a lipopolysaccharide (LPS) derived from Pantoea agglomerans is effective in an intraoral mucous membrane, ocular mucous membrane, ear mucous membrane, genital mucous membrane, pharyngeal mucous membrane, respiratory tract mucous membrane, bronchial mucous membrane, pulmonary mucous membrane, gastric mucous membrane, enteric mucous membrane, or rectal mucous membrane from the example of the vaccine containing a lipopolysaccharide (LPS) derived from Pantoea agglomerans described in Patent Literature 3.